Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033774 (pruritus)
 14,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The topical calcineurin inhibitors (TCIs) pimecrolimus and tacrolimus are approved for atopic dermatitis but have additional potential in other inflammatory skin diseases. This article reviews their clinical use in non-atopic dermatitis diseases. In seborrheic dermatitis, asteatotic eczema, and contact dermatitis, TCIs are of great benefit and can compete with topical corticosteroids. In psoriasis, TCIs have shown clinical efficacy and safety in facial and intertriginous lesions. Further investigations into possible combinations of TCIs with other established treatments such as UVB irradiation in this disorder are necessary. Initial studies in cutaneous lupus erythematosus have been promising, whereas the response in rosacea and rosacea-like eruptions has been mixed. TCIs have been associated with good clinical responses in oral lichen planus and anogenital lichen sclerosus et atrophicus. In vitiligo, TCIs are associated with some degree of repigmentation, with better results being seen in children and in facial and neck areas. TCIs have a synergistic effect with UVB irradiation in vitiligo. There is a long list of small series and case reports documenting use of TCIs in various other skin conditions that warrant further validation. Although the established mode of action of TCIs is T-cell control, other effects also need to be considered. Specifically, TCIs reduce pruritus and erythema, which cannot be explained by T-cell interactions, and further investigations are needed in these fields.
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PMID:The role of topical calcineurin inhibitors for skin diseases other than atopic dermatitis. 1749 44

Tacrolimus is an ascomycin macrolactam derivative with immunomodulatory and anti-inflammatory activity that belongs to the class of calcineurin inhibitors. Tacrolimus in its topical formulation has been established as a safe and effective alternative to topical corticosteroids because of its mild side effects and its minimal systemic absorption. Topical tacrolimus has been approved for the treatment of atopic dermatitis in two concentrations, 0.03 and 0.1%. In a thorough research of literature the authors review all of the available data regarding the off-label uses of the medication in other dermatoses. It seems that compared to pimecrolimus, tacrolimus has proved to be a more effective treatment. There is no causal relationship that has been established between tacrolimus and carcinogenesis. Furthermore, the authors believe that, without any evidence, the theoretical concerns are not enough to produce warnings. Tacrolimus ointment 0.1% may be recommended as a first-line choice for seborrheic dermatitis of the face and trunk, facial and intertriginous psoriasis and probably for allergic contact dermatitis and Zoon's balanitis. It has been ineffective in numerous dermatoses such as alopecia areata, necrobiosis lipoidica, internal pruritus and in thick hyperkeratotic plaques of psoriasis when administered as the commercially available formulation without occlusion. There is yet unexploited therapeutic potential regarding the use of topical tacrolimus in dermatology. Isolated cases of successful administration of the medication in various cutaneous conditions require further large-scale studies to clarify the actual effectiveness.
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PMID:Assigning new roles to topical tacrolimus. 1768 74

The ubiquitination system comprises a highly specific and regulated post-translational mechanism by which the immune response can be modulated, setting the balance between immunity and tolerance. Proteolysis dependent and independent mechanisms have been implicated. Particularly, the role of ubiquitin ligases as modulators of central and peripheral tolerance has brought attention to this system as one of the key elements of a complex regulatory network designed to maintain an active surveillance system. Cbl-b, GRAIL and Itch are the main E3 ligases, considered as negative regulators of the immune response as part of the genetic program induced by the calcium/calcineurin pathway. Other key signaling pathways for the immune response, such as the NF-kappaB and TGF-beta signaling are prone to be modulated by these ubiquitin ligases. Diverse mechanisms have been implicated in the development of anergy associated to E3 ligases, among these, the setting for TCR responsiveness and repression of cytokine transcription are best well characterized. Also, a role as inductors of regulatory T cells has been evidenced for Cbl-b and GRAIL. The defective expression of some of these E3 ligases has been related to the development of autoimmune disease, in experimental murine and human models, remarking its possible pathogenic role.
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PMID:Ubiquitination system and autoimmunity: the bridge towards the modulation of the immune response. 1829 31

Atopic dermatitis is a chronic inflammatory skin disease characterized by recurrent intense pruritus and a distinctive distribution of skin lesions. The topical calcineurin inhibitors tacrolimus and pimecrolimus were approved in the USA, as an ointment and a cream, respectively, for the treatment of atopic dermatitis in 2000 and 2001, respectively. In 2005, the Pediatric Advisory Committee of the US FDA implemented a 'black box' warning for tacrolimus ointment and pimecrolimus cream due to the lack of long-term safety data and the potential risk of the development of malignancies. This article focuses on the safety aspects of these agents by discussing the findings from preclinical and clinical studies and postmarketing reports with regard to malignancies occurring after the use of tacrolimus ointment and pimecrolimus cream.
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PMID:The US FDA 'black box' warning for topical calcineurin inhibitors: an ongoing controversy. 1830 44

The introduction of topical calcineurin inhibitors resulted in a significant improvement in the treatment of atopic dermatitis. In addition, rapid amelioration of pruritus could be observed. In case reports, other pruritic dermatoses such as chronic irritative hand dermatitis, rosacea, graft-versus-host-disease, and lichen sclerosus were also treated successfully with pimecrolimus and tacrolimus. Twenty patients were treated with tacrolimus and pimecrolimus in a surveillance study to evaluate efficacy in pruritus and prurigo. Eighteen of 20 patients responded to therapy. Best results were obtained in localized and generalized pruritus while in prurigo nodularis only a subgroup of patients showed an improvement of pruritus. Further controlled studies are necessary to confirm these results.
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PMID:Treatment of pruritic diseases with topical calcineurin inhibitors. 1836 May 95

Plasma cell balanitis of Zoon is a chronic, benign, inflammatory dermatosis of the glans penis and prepuce. The exact aetiology is unknown. The treatments described to date have provided only partially successful results. Recently, several reports of plasma cell balanitis successfully treated with calcineurin inhibitors have been published. We report 3 cases of plasma cell balanitis refractory to several treatments with steroids and antifungals treated with pimecrolimus 1% cream applied twice daily: 1 patient had a complete resolution, 1 patient had a marked response but relapsed during the treatment and the last patient had a partial response due to the development of a side effect that precociously required to stop the treatment. One patient referred a slight pruritus after the first applications of the cream that spontaneously disappeared after a few minutes. Additional experiences are needed to determine if topical pimecrolimus is an effective and safe treatment for plasma cell balanitis.
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PMID:Discordant results with pimecrolimus 1% cream in the treatment of plasma cell balanitis. 1883 8

We present the 12-month results of a prospective trial of conversion from calcineurin inhibitors (CNI) to everolimus (EVL) in maintenance liver transplant (LT) recipients. Forty (M:F = 28:12; 54.9 +/- 11 years) patients were enrolled at a mean interval of 45.5 +/- 31.2 months from transplantation. Conversion was with EVL at a dosage of 0.75 mg b.i.d., withdrawal of antimetabolites, and a 50%-per-week reduction of CNI to a complete stop within 4 weeks. The treatment success was conversion to EVL monotherapy at 12 months while failure was presence of CNI, death, and graft loss. Indication to conversion was deteriorating renal function in 36 (90%). At 12 months, patient- and graft survival were 100% and the success rate was 75% (30/40). Ten patients (25%) were failures: four (10%) for acute rejection; three hepatitis C virus-RNA positive patients (7.5%) for hypertransaminasemia; one (2.5%) for acute cholangitis; and two (5%) due to persistent pruritus and oral ulcers. In patients on EVL monotherapy, at 12 months the mean change of calculated creatinine clearance (cCrCl) was 4.03 +/- 12.6 mL/min and the only variable correlated with the probability of improvement was baseline cCrCl (P < 0.0001). Conversion from CNI to EVL is feasible in 75% of the cases and associated with improvement in renal function for patients with higher baseline cCrCl.
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PMID:Conversion to everolimus monotherapy in maintenance liver transplantation: feasibility, safety, and impact on renal function. 1905 83

EpiCeram consists of a specific combination of ceramides, cholesterol and fatty acids that mimics those naturally found in the skin. EpiCeram was approved by the FDA in April 2006 for use as a nonsteroidal lipid barrier emulsion to manage symptoms of burning and itching associated with dry skin conditions such as atopic dermatitis, irritant contact dermatitis, radiation dermatitis and other dermatoses. EpiCeram has shown comparable efficacy to a mid-strength topical corticosteroid in a clinical study involving 113 children with moderate to severe atopic dermatitis. Unlike topical steroids and immunomodulators such as calcineurin inhibitors that have clinically well-recognized undesirable side effects and usage restrictions (including FDA black box warning for the latter), current data suggests that EpiCeram has a favorable safety profile. Additionally, EpiCeram does not appear to have substantial restrictions associated with its use, especially with regards to the duration of use or patient age, compared to the other classes of prescription products.
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PMID:Epiceram for the treatment of atopic dermatitis. 1913 28

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease, affecting 10-20% of children and 2% of adults worldwide. Preventive treatment of AD consists of daily skin hydration and emollient therapy; but the majority of patients still require symptomatic treatment with topical corticosteroids and/or topical calcineurin inhibitors, both of which may be associated with potential long-term side effects. With increasing evidence supporting the role of skin barrier defects in the pathogenesis of AD, there is also a parallel increase in medications that claim to assist barrier repair. The current review discusses some exciting results with these medications, as well as the challenges that lie ahead of them. While barrier repair treatments offer some promise, there continues to be a need for safer anti-inflammatory medications. Some of these medications under investigation are phosphodiesterase-4 inhibitors, urocanic acid oxidation products and IL-4/IL-13 receptor blockers. The review also discusses anti-staphylococcal treatments including nanocrystalline silver cream, silver and antimicrobial-coated fabrics, and anti-itch treatments including mu-opiod receptor antagonists, chymase inhibitors and cannabinoid receptor agonists. These medications may become an integral part of AD therapy.
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PMID:Emerging drugs for atopic dermatitis. 1921 4

Pruritus (itch) is an unpleasant sensation inducing the desire to scratch. Chronic pruritus (>6 weeks' duration) is a major and distressing symptom of many diseases of dermatological, systemic, neurological or psychogenic origin. Frequently, the underlying cause of pruritus cannot be identified and causal therapy is not possible. Furthermore, chronic pruritus is frequently refractory to conventional symptomatic therapies. Recent research has revealed new neuronal mechanisms in the skin and brain, suggesting novel therapeutic targets. The efficacy of the corresponding innovative therapies has been proven in recent studies and case series. For example, topical or systemic application of specific agonists such as cannabinoids or calcineurin inhibitors can influence neuroreceptors on sensory nerve fibers of the skin and suppress pruritus. Itch-selective neurons in the dorsal horn of the spinal cord can be targeted to inhibit the transmission of pruritus to the somatosensory cortex. Anticonvulsants, antidepressants and micro-opioid receptor antagonists interfere with the sensation of pruritus in the central nervous system. Chronic pruritus of any origin leads to considerable psychosocial burden and impairs quality of life. Psychoeducational interventions, stress training, training in social competence and relaxation techniques are therefore important elements in the treatment of chronic pruritus. Increasing knowledge of the neurobiology of chronic pruritus offers new therapeutic strategies. Currently, several clinical trials are investigating the efficacy of new substances addressing neuroreceptors and cytokines in the skin and central nervous system. The present review aims to provide an overview of current neurophysiological and neurochemical therapeutic models in chronic pruritus.
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PMID:Chronic pruritus: targets, mechanisms and future therapies. 1922 35


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